Abstract We propose a rigorous randomized trial to evaluate an innovative stepped care for suicide prevention intervention for adolescents and young adults, compared to a ZS program initiated by a health system. An effective ZS strategy for this age group is critically needed because this is a developmental period when: 1) suicide is the second leading cause of death, accounting for more deaths than any medical illness; 2) suicidal tendencies and behaviors often first occur in this age span; 3) rates of suicide and suicide attempts (SAs) increase dramatically; and 4) effective intervention can reduce risk, suffering, and costs over lifetimes. The project combines a partnership with a health system that has strong infrastructure and commitment to quality improvement for ZS with a research team that has successfully implemented collaborative stepped care interventions in health systems and has expertise in clinical, health services, economics, and policy research and dissemination. We will identify and enroll 300 youths ages 12-24 with elevated suicide and SA risk using a multi-stage screening process. Eligible youths will be randomized to: 1) zero suicide best practices, which emphasizes health system quality improvement using the zero suicide toolkit (ZSBP, www.sprc.org); or 2) ZSBP+ stepped care for suicide prevention, which integrates evidence-based suicide prevention with primary care and emergency services. Prior research demonstrates the value of similar integrated medical- behavioral health interventions for improving patient outcomes, rates of care, and continuity of care- a critical issue for ZS efforts, as many youths discontinue care prematurely despite continuing risk. The ZSBP+ approach uses: 1) risk assessments to triage youths to appropriate care levels; 2) Care Managers to deliver CBT and DBT skills training and support primary care and emergency clinicians with patient evaluation and treatment; 3) internet eCBT and therapeutic DBT skills video plus access to coaching support (24/7) for lower risk youths, with stepped up in-person group and/or individual treatment added for higher risk youths; and 4) regular monitoring of patient outcomes, with real-time feedback to clinicians to facilitate decision-making and use of the stepped care algorithms. The intervention period is 12 months: 6 months of acute treatment; and 6 months of continuation treatment. Outcomes are assessed at baseline and at 3, 6 and 12-month follow-ups. We hypothesize that, compared to youths in ZSBP, youths randomized to ZSBP+ will have significantly lower rates of fatal and nonfatal SAs over time (primary outcome) and will show improvements on secondary outcomes (suicide events over time, self-harm episodes, depressive symptoms). We will also conduct cost effectiveness analyses. Results will provide critical information for health systems and science regarding the potential to achieve ZS goals by integrating state of the art science with practice quality improvement. ZSBP+ stepped care for suicide prevention has potential for broader sustained adoption within the health system and national dissemination, enhancing our capacity to meet the ZS challenge.